[gmx-users] ASN instead of ASP in the binding site: how to find the novel complex conformation ?

[Luca Mollica]

Dear all,

I am simulating protein dimer both without and with the ligand in the 
binding site. The structure that I got from PDB has the ligand (a 
molecule of ASP) in the binding site, and my goal is to simulate the 
dynamics of the protein without the ligand and with a novel but similar 
ligand (a molecule of ASN) that was put in the same position of the old 
ligand but randomly oriented (in order to avoid any bias). The 
simulation of the dimer without ligand was fine, but I have encountered 
a big trouble during the ligand-dimer complex simulation, realising that 
after 600-700 ps there was a separation of the two monomer, a loss in 
sec.strucure and an almost stepwise increase of the radius of gyration 
(also, the complex starts to rotate around an axis with great speed).

Therefore, I have two questions:

1. Could anyone provide me an explanation for a strange event like 
rotation ?
2. I am also thinking to use another approach to the problem, keeping 
protein atomic positions restrained except the ones in the binding site: 
  what do you think about it? Should I keep all the positions restrained ?

The simulations have been performed using pbc, cut off electrostatics, 
GROMACS FF and with implicit solvent (these are preliminary simulations).

Thanx

LM



................................................................................................

Luca Mollica
Dulbecco Telethon Institute (Biomolecular NMR Lab)

DIBIT-HSR,Via Olgettina 58, 1B4
20132 Milano (Italy)

Tel: 0039-02-26434824(Office)/26433497(Lab)
Fax: 0039-02-26434153
E-mail: mollica.luca at hsr.it


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